Crystal structures of H-2Db in complex with the LCMV-derived peptides GP92 and GP392 explain pleiotropic effects of glycosylation on antigen presentation and immunogenicity

Post-translational modifications significantly broaden the epitope repertoire for major histocompatibility class I complexes (MHC-I) and may allow viruses to escape immune recognition. Lymphocytic choriomeningitis virus (LCMV) infection of H-2b mice generates CD8+ CTL responses directed towards seve...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2017, Vol.12 (12), p.e0189584-e0189584
Main Authors: Hafstrand, Ida, Badia-Martinez, Daniel, Josey, Benjamin John, Norström, Melissa, Buratto, Jérémie, Pellegrino, Sara, Duru, Adil Doganay, Sandalova, Tatyana, Achour, Adnane
Format: Article
Language:English
Subjects:
Antigen presentation
Antigens
Asparagine
Binding
Biology and Life Sciences
CD8 antigen
Chromatography
Crystal structure
Cytotoxicity
Epitopes
Glycosylation
Histocompatibility antigen H-2
Hospitals
Immunogenicity
Infectious diseases
Laboratories
Lymphocytes
Lymphocytes T
Major histocompatibility complex
Mass spectrometry
Medicin och hälsovetenskap
Medicine
Medicine and Health Sciences
Pathogens
Peptides
Physical Sciences
Polypeptides
Post-translation
Proteins
Scientific imaging
Translation
Tumors
Viral infections
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Post-translational modifications significantly broaden the epitope repertoire for major histocompatibility class I complexes (MHC-I) and may allow viruses to escape immune recognition. Lymphocytic choriomeningitis virus (LCMV) infection of H-2b mice generates CD8+ CTL responses directed towards several MHC-I-restricted epitopes including the peptides GP92 (CSANNSHHYI) and GP392 (WLVTNGSYL), both with a N-glycosylation site. Interestingly, glycosylation has different effects on the immunogenicity and association capacity of these two epitopes to H-2Db. To assess the structural bases underlying these functional results, we determined the crystal structures of H-2Db in complex with GP92 (CSANNSHHYI) and GP392 (WLVTNGSYL) to 2.4 and 2.5 Å resolution, respectively. The structures reveal that while glycosylation of GP392 most probably impairs binding, the glycosylation of the asparagine residue in GP92, which protrudes towards the solvent, possibly allows for immune escape and/or forms a neo-epitope that may select for a different set of CD8 T cells. Altogether, the presented results provide a structural platform underlying the effects of post-translational modifications on epitope binding and/or immunogenicity, resulting in viral immune escape.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0189584